Role of Human Cerebrospinal Fluid Chemokines in the Invasiveness of Human Glioblastoma

项目摘要 胶质母细胞瘤（GBM）是成人中最常见的、侵袭性的和增殖性的原发性脑肿瘤，尽管目前的研究表明， 结合联合收割机手术、放疗和化疗的治疗策略。GBM的高侵袭能力使总的 手术切除几乎不可能，导致极高的复发率。形成新肿瘤的能力 存在于GBM内称为脑肿瘤起始细胞（BTIC）的细胞亚群中。BTIC未分化 具有自我更新和多能性能力的细胞，还具有在体内形成肿瘤的能力。本集团与 其他人报道，在原发性GBM中，那些位于侧脑室（LV）附近的GBM 多个不同的特征，包括远处复发增加，这对患者的生存产生了负面影响。 左心室近端GBM患者结局恶化的原因尚不清楚。可能的解释可能 涉及这些肿瘤接近脑脊液（CSF）和脑室下区的神经源性龛 （SVZ）。在初步研究中，我们已经确定人非癌CSF在体外排斥BTIC迁移。的分子 在CSF中负责这种影响是未知的。在这里，我们建议研究BTIC之间的相互作用， CSF的不同部分。我们假设CSF可以诱导GBM细胞更具攻击性的行为。我们将 使用术中人体组织进行这项研究。完成这项研究后，我们将获得更好的 了解CSF对GBM细胞的影响，并将发现CSF中影响GBM细胞的可能因素。 BTIC和癌症进展。最终，我们希望揭示治疗干预的具体目标， GBM患者的生存率增加。

PROJECT SUMMARY Glioblastoma (GBM) is the most common, aggressive and proliferative primary brain tumor in adults despite current therapeutic strategies that combine surgery, radio, and chemotherapy. The high invasive capacity of GBM makes total surgical resection virtually impossible, resulting in an extremely high recurrence rate. The ability to form a new tumor resides in a subpopulation of cells within the GBM called brain tumor initiating cells (BTICs). BTICs are undifferentiated cells with self-renewing and pluripotential capacity, with the added ability of forming tumors in vivo. Our group and others have reported that among primary GBMs, those located in close proximity to the lateral ventricles (LV) present multiple distinct features, including increased recurrence at distant locations, which negatively affect patients' survival. The cause for worse outcomes in patients suffering LV-proximal GBMs is not known. Possible explanations may involve the proximity of these tumors to the cerebrospinal fluid (CSF) and neurogenic niche in the sub-ventricular zone (SVZ). In a pilot study, we have determined that human non-cancer CSF repels BTICs migration in vitro. The molecules in the CSF responsible for this effect are not known. Here we propose to study the interactions between BTICs and different fractions of CSF. We hypothesize that CSF can induce a more aggressive behavior of GBM cells. We will perform this research using intraoperative human tissue. Upon completion of this study we will have gained a better understanding of the effects of CSF on GBM cells and will have discovered possible factors within CSF which influence BTICs and cancer progression. Ultimately, we hope to reveal specific targets for therapeutic intervention leading to increased survival in patients with GBM.